Use of insulin degrading enzyme (IDE) for the treatment of alzheimer's disease in patients

Abstract

The peptidase insulin degrading enzyme (IDE) has been shown to cleave Aβ peptides. Cleavage of Aβ 1-42 by recombinant IDE abolishes its cell toxicity. Recombinant IDE is expressed on the surface of cells or secreted from cells in plaque forming regions of the brain. Primary hippocampal and cortical cells are treated with Aβ peptides in the presence or absence of IDE and cell toxicity measured. Cells are recombinantly engineered to express IDE on the cell surface or secrete it. The membrane bound and secreted forms of IDE are then expressed in a mammal.

What is claimed is:  
     
         1 . A method for preventing formation or growth of amyloid fibrils or plaques without causing neurotoxicity, comprising administering an inactivating effective amount of an amyloid peptide inactivating enzyme to a mammal in need thereof.  
     
     
         2 . The method according to  claim 1 , wherein said enzyme is a peptidase.  
     
     
         3 . The method according to  claim 2 , wherein said enzyme is insulin degrading enzyme (IDE) or neprilysin or endopeptidase 24.15, endopeptidase 24.16, or similar peptidases.  
     
     
         4 . The method according to  claim 1 , wherein said amyloid peptide is Aβ.  
     
     
         5 . The method according to  claim 4 , wherein said Aβ protein is Aβ 1-40  or Aβ 1-42 .  
     
     
         6 . The method according to  claim 1 , wherein said mammal is human.  
     
     
         7 . A method for preventing formation or growth of amyloid plaque without causing neurotoxicity, comprising: 
 a) generating a recombinant viral or plasmid vector comprising a DNA sequence encoding an amyloid peptide inactivating enzyme operatively linked to a promoter;    b) transfecting in vitro a population of cultured neural cells with said recombinant vector, resulting in a population of transfected neural cells; and    c) transplanting said transfected neural cells by injection to the brain of a mammalian host, such that expression of said DNA sequence within said brain results in inactivation of said amyloid peptides.    
     
     
         8 . The method according to  claim 7 , wherein said neural cells are hippocampal or cortical cells.  
     
     
         9 . The method according to  claim 7 , wherein said enzyme is a peptidase.  
     
     
         10 . The method according to  claim 9 , wherein said peptidase is insulin degrading enzyme (IDE) or neprilysin.  
     
     
         11 . The method according to  claim 7 , wherein said amyloid peptide is Aβ.  
     
     
         12 . The method according to  claim 11 , wherein said Aβ protein is Aβ 1-40  or Aβ 1-42 .  
     
     
         13 . The method according to  claim 7 , wherein said brain is the cortex or hippocampus.  
     
     
         14 . A method for preventing formation or growth of amyloid plaque without causing neurotoxicity, comprising: 
 a) generating a recombinant viral or plasmid vector comprising a DNA sequence encoding an amyloid peptide inactivating enzyme operatively linked to a promoter; and    b) injecting said vector to the brain of a mammalian host, such that expression of said DNA sequence within said brain results in inactivation of said amyloid peptides.    
     
     
         15 . A method for preventing formation or growth of amyloid plaque without causing neurotoxicity, comprising administering to a patient in need thereof a compound that enhances the expression of the amyloid inactivating enzyme.  
     
     
         16 . The method according to  claim 15 , wherein said enzyme is IDE or neprilysin.  
     
     
         17 . The method according to  claim 15 , wherein said enhancement of expression of the amyloid inactivating enzyme occurs at the gene expression level.  
     
     
         18 . The method according to  claim 17 , wherein said compound is a transactivator of said amyloid inactivating enzyme.